Opinion statementRecently introduced systemic therapies for locally advanced and metastatic non-melanoma skin cancers (NMSCs) are paving the way for neoadjuvant approach. Although none of the therapeutic options has currently gained indication in this setting, neoadjuvant approach for NMSCs is an open field and we are likely to see huge developments in the near future. Targeted therapy with sonic hedgehog pathway inhibitors is very effective in locally advanced or multiple basal cell carcinomas while immunotherapy with immune checkpoint inhibitors appears to be promising for advanced cutaneous squamous cell carcinoma and Merkel cell carcinoma. To date, targeted therapy and immunotherapy represent the frontiers in NMSC therapeutic management and, according to recent studies, good results can be achieved.
Background: Non-melanoma skin cancer (NMSC) stands as an umbrella term for common cutaneous malignancies, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together with rarer cutaneous cancers, such as Merkel cell carcinoma (MCC) and other forms of adnexal cancers. The majority of NMSCs can be successfully treated with surgery or radiotherapy, but advanced and metastatic stages may require systemic approaches such as immunotherapy with immune checkpoint inhibitors (ICIs). Summary: Since immunotherapy is not effective in all patients and can potentially lead to severe adverse effects, an important clinical question is how to properly identify those who could be suitable candidates for this therapeutic choice. In this paper, we review the potential features and biomarkers used to predict the outcome of ICIs therapy for NMSCs. Moreover, we analyze the role of immunotherapy in special populations, such as the elderly, immunocompromised patients, organ transplant recipients, and subjects suffering from autoimmune conditions. Key messages: Many clinical, serum, histopathological, and genetic features have been investigated as potential predictors of response in NMSCs treated with ICIs. Although this field of research is very promising, definitive, cost-effective, and reproducible biomarkers are still lacking and further efforts are needed to validate the suggested predictors in larger cohorts.
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